Role of astrocytic connexins in health and disease

Abstract

Despite of the growing number of studies, the expression pattern as well as the exact functions of astrocytic connexins are not yet fully elucidated. In this study I analyzed the expression pattern and functions of the two major astrocytic connexins, Cx30 and Cx43, under normal conditions and in a mouse model for temporal lobe epilepsy (TLE).<br /> In the first part of my work I characterized novel conditional knock out mice, expressing ECFP instead of Cx43 after Cre-mediated recombination. Utilizing this mouse, I demonstrated dual reporter approaches to i) simultaneously examine astrocyte subpopulations expressing different connexins, ii) identify compensatory upregulation within gene families and iii) quantify Cre-mediated deletion at the allelic level.<br /> In the second part of my work, I re-evaluated the expression of Cx30 in different brain regions. I analyzed the reporter gene expression of Cx30 knockout mice. Utilizing a fate mapping approach, I showed that the reporter gene expression does not reflect properly the Cx30 expression in the hippocampus. Using a fate mapping approach, I also demonstrated that Cx30 is expressed at similar levels compared to Cx43 in most brain regions. In addition, utilizing the same fate mapping approach, I showed that radial glia like cells express mostly Cx43, indicating that Cx43 is the most important connexin for adult neurogenesis.<br /> In the third part of my work, I analyzed the influence of Cx30 and Cx43 on morphological changes in brain of mice subjected to a novel mouse TLE model (intracortical kainate injection). In mice lacking both Cx43 and Cx30, I observed less pronounced morphological changes in the hippocampus. I also established methods for quality control of the trangenic mice used in this study. My study adds to a better understanding of expression pattern of astrocytic connexines in the brain, and its role in the epilepsy.